Functional cartilage repair continues to be a challenging issue faced by clinicians and scientists alike. The long-term objective of our research is to regenerate functional cartilage over a large area of an articular surface with sufficient hyaline qualities that give the new tissue the capacity to survive long-term. This application will assess the hondrogenic potential of a cartilage construct, created via tissue engineering techniques, in two in vivo models for cartilage repair. The tissue engineered construct, demonstrated in vitro to have exciting chondrogenic capabilities, consists of a polylactic acid/alginate amalgam seeded with bone marrow-derived cells. The first in vivo model is a widely used system in which new cartilage is grown in cylindrical osteochondral defects. The second model is well-developed and has generated substantial quantities of cartilage on the patellar surface by modulation of the biomechanical environment. Biomechanical stresses which are part of normal joint function are removed from the patellar surface by inserting spacers in the patellae. Relief of the stress is temporary, however it is only necessary during initial stages of chondrogenesis (the 6 week time frame studied here) when the tissue may be easily damaged. In vivo experiments will be undertaken with three associated specific aims. Specific Aim 1: evaluate the in vivo chondrogenic potential of a tissue engineered cartilage construct, with and without seeded cells, in osteochondral defects. Specific Aim 2: apply this construct on a large, clinically relevant, surface and regenerate cartilage with the aid of stress shielding. Specific Aim 3: apply this construct on the large surface to regenerate cartilage with stress shielding, followed by reinstating the normal stress environment on the surface to assess the regenerated tissue?s capacity for survival and remodeling. The regenerated cartilage will be evaluated by three sets of analyses: a) histological; b) immunolocalization and c) biomechanical. Success of these in-vivo, dynamic models will provide a useful means for regenerating cartilage on articular surfaces subjected to severe mechanical loads. It can help pave the way for many clinical applications.